Conventional dendritic cells are the critical donor APC presenting alloantigen after experimental bone marrow transplantation

KA Markey, T Banovic, RD Kuns… - Blood, The Journal …, 2009 - ashpublications.org
KA Markey, T Banovic, RD Kuns, SD Olver, ALJ Don, NC Raffelt, YA Wilson, LJ Raggatt…
Blood, The Journal of the American Society of Hematology, 2009ashpublications.org
We have quantified the relative contribution of donor antigen-presenting cell populations to
alloantigen presentation after bone marrow transplantation (BMT) by using transgenic T
cells that can respond to host-derived alloantigen presented within the donor major
histocompatibility complex. We also used additional transgenic/knockout donor mice and/or
monoclonal antibodies that allowed conditional depletion of conventional dendritic cells
(cDCs), plasmacytoid DC (pDCs), macrophages, or B cells. Using these systems, we …
We have quantified the relative contribution of donor antigen-presenting cell populations to alloantigen presentation after bone marrow transplantation (BMT) by using transgenic T cells that can respond to host-derived alloantigen presented within the donor major histocompatibility complex. We also used additional transgenic/knockout donor mice and/or monoclonal antibodies that allowed conditional depletion of conventional dendritic cells (cDCs), plasmacytoid DC (pDCs), macrophages, or B cells. Using these systems, we demonstrate that donor cDCs are the critical population presenting alloantigen after BMT, whereas pDCs and macrophages do not make a significant contribution in isolation. In addition, alloantigen presentation was significantly enhanced in the absence of donor B cells, confirming a regulatory role for these cells early after transplantation. These data have major implications for the design of therapeutic strategies post-BMT, and suggest that cDC depletion and the promotion of B-cell reconstitution may be beneficial tools for the control of alloreactivity.
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